S228: POSITRON EMISSION TOMOGRAPHY EVALUATION IN A LARGE GROUP OF PATIENTS AFFECTED BY RELAPSED/REFRACTORY B-CELL LYMPHOMAS TREATED WITH ANTI-19 CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELLS THERAPY (CART SIE).
Authors: Anna Dodero, Anna Guidetti, Annalisa Chiappella, Silva Ljevar, Martina Pennisi, Pier Luigi Zinzani, Beatrice Casadei, Stefania Bramanti, Armando Santoro, Patrizia Chiusolo, Alice DI Rocco, Martina DI Palma, Maria Chiara Tisi, Ilaria Cutini, Matteo Carrabba, Maurizio Musso, Massimo Martino, Anna Maria Barbui, Mattia Novo, Giovanni Grillo, Martalisa Battista, Manuela Zanni, Luca Arcaini, Rosalba Miceli, Martina Magni, Cristiana Carniti, Paolo Corradini
Journal: HemaSphere (2023)

Background: CD19 direct chimeric antigen receptor (CAR) T-cell therapy is an effective therapy for patients (pts) affected by relapsed/refractory (R/R) large B-cell lymphomas (LBCL). Positron emission tomography/computed tomography (PET/CT) is used early post CAR T-infusion but the prognosis of pts with partial or stable disease at 1-month is less define. Aims: The objective of the study was to analyze the role of early PET/CT in combination with pre-infusion biomarkers to determine long-term outcome. Methods: CART-SIE is an ongoing prospective and retrospective observational study evaluating the outcome of pts treated with CAR T-cells. From March 2019 to December 2022, 499 patients were enrolled. In this study we included only pts with adequate follow-up (30 days) and an FDG-PET/CT before infusion (PET-0), at 1 month (PET-1) and at 3 months (PET-3) after CAR-T cells infusion. A landmark analysis based on PET-1 result was performed for Progression-free survival (PFS) and Overall Survival (OS) estimation. Results: Two hundred and twenty-one pts with R/R LBCL [n= 129 Diffuse large B-cell lymphomas, n= 39 High-grade B-cell lymphomas (HGBCL), n= 27 Primary Mediastinal B-cell lymphomas (PMBCL), n= 26 Mantle Cell Lymphoma (MCL)] received CAR T-cell treatment with axicabtagene-ciloleucel (n=103, axicel), tisagenlecleucel (n=93, tisacel) and brexucabtagene autoleucel (n=25, brexucel). The median age of the pts was 57 years (64 pts were older of 65 years). Most of the pts [n=184(83%)] were treated with a bridging therapy. Bulky and extranodal disease were observed in 72(32%) and 125(56%) of the pts, respectively. Evaluation of pre-lymphocytoapheresis absolute lymphocyte value and PCR were evaluable for 199 (90%) and 183 (83%) pts, respectively. The median follow-up time was 11 months. At the time of PET-1, 116 pts (52%) showed a PET with DS1-3, 52 (24%) had a PET with DS 4 (n=38 PR, n=14 SD) and 53 (24%) with DS5 (n=16 SD, n=37 PD). At the time of PET-3, 11 of 52 (21%) DS4 and 3 of 53 (6%) DS5 at PET-1 converted in CR. The 1-year PFS based on PET-1 was 67%, 42% and 8% for DS1-3, DS4 and DS5 (p<0,0001), respectively. The 1-year OS based on PET-1 was 90%, 83% and 37% for DS1-3, DS4 and DS5, respectively. Multivariable analyses identified DS5 value at day 30 and CAR T-cell product Tisacel associated to increase risk of failure (HR: 11.03; 95%CI 5.47-22.21, p<0.0001; 1.79; 95%CI: 0.98-3.27; p<0.0586) whereas higher lymphocyte count at lymphocytoapheresis improved outcome (HR: 0.65; 95%CI: 0.46-0.90; p<0.0101). Summary/Conclusion: The 1-year PFS of pts with DS4 at PET-1 was only 42% suggesting the need of early salvage treatment in these pts and integration with biological markers to help in predicting the progression risk; pts with DS5 had a very poor outcomeKeywords: Positron emission tomography (PET), CAR-T